Gene expression analysis of the endocannabinoid system in presymptomatic APP/PS1 mice

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• dc.contributor.author Vidal-Palencia, Laura
• dc.contributor.author Ramon Duaso, Carla, 1987-
• dc.contributor.author González-Parra, Jose Antonio
• dc.contributor.author Busquets Garcia, Arnau, 1985-
• dc.date.accessioned 2022-09-20T06:05:19Z
• dc.date.available 2022-09-20T06:05:19Z
• dc.date.issued 2022
• dc.description.abstract Alzheimer's disease (AD) is the most common type of dementia and neurodegeneration. The actual cause of AD progression is still unknown and no curative treatment is available. Recently, findings in human samples and animal models pointed to the endocannabinoid system (ECS) as a promising therapeutic approach against AD. However, the specific mechanisms by which cannabinoid drugs induce potential beneficial effects are still undefined. For this reason, it is required a full characterization of the ECS at different time points of AD progression considering important factors such as sex or the analysis of different brain regions to improve future cannabinoid-dependent therapies in AD. Thus, the main aim of the present study is to expand our knowledge of the status of the ECS in a presymptomatic period (3 months of age) using the AD mouse model APP/PS1 mice. First, we evaluated different behavioral domains including anxiety, cognitive functions, and social interactions in male and female APP/PS1 mice at 4 months of age. Although a mild working memory impairment was observed in male APP/PS1 mice, in most of the behaviors assessed we found no differences between genotypes. At 3 months of age, we performed a characterization of the ECS in different brain regions of the APP/PS1 mice considering the sex variable. We assessed the expression of the ECS components by quantitative Real-Time Polymerase Chain Reaction in the hippocampus, prefrontal cortex, hypothalamus, olfactory bulb, and cerebellum. Interestingly, gene expression levels of the type-1 and type-2 cannabinoid receptors and the anabolic and catabolic enzymes, differed depending on the brain region and the sex analyzed. For example, CB1R expression levels decreased in both hippocampus and prefrontal cortex of male APP/PS1 mice but increased in female mice. In contrast, CB2R expression was decreased in females, whereas males tended to have higher levels. Overall, our data indicated that the ECS is already altered in APP/PS1 mice at the presymptomatic stage, suggesting that it could be an early event contributing to the pathophysiology of AD or being a potential predictive biomarker.
• dc.description.sponsorship This work was supported by a funded project from the Agencia Estatal de Investigación-FEDER (RTI2018-093667-A-100) and the IBRO Return Home Fellowships 2019 received by AB-G. AB-G is a Ramon y Cajal researcher (RYC-2017-21776, funded by MCIN/AEI/10.13039/501100011033 and FSE). LV-P is a FI predoctoral fellow (2021 FI_B 00133) from the Generalitat de Catalunya (AGAUR).
• dc.format.mimetype application/pdf
• dc.identifier.citation Vidal-Palencia L, Ramon-Duaso C, González-Parra JA, Busquets-Garcia A. Gene expression analysis of the endocannabinoid system in presymptomatic APP/PS1 mice. Front Pharmacol. 2022 Mar 18;13:864591. DOI: 10.3389/fphar.2022.864591
• dc.identifier.doi http://dx.doi.org/10.3389/fphar.2022.864591
• dc.identifier.issn 1663-9812
• dc.identifier.uri http://hdl.handle.net/10230/54114
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Pharmacol. 2022 Mar 18;13:864591
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-093667-A-100
• dc.rights © 2022 Vidal-Palencia, Ramon-Duaso, González-Parra and Busquets-Garcia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword APP/PS1 mice
• dc.subject.keyword Alzheimer Disease
• dc.subject.keyword CB1 receptors
• dc.subject.keyword Brain-region analysis
• dc.subject.keyword Mouse behaviour
• dc.subject.keyword Sex-dependent
• dc.title Gene expression analysis of the endocannabinoid system in presymptomatic APP/PS1 mice
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion